Conflict-related health research in Syria, 2011–2019: a scoping review for The Lancet - AUB Commission on Syria

Background The volume of health-related publications on Syria has increased considerably over the course of the conflict compared with the pre-war period. This increase is largely attributed to commentaries, news reports and editorials rather than research publications. This paper seeks to characterise the conflict-related population and humanitarian health and health systems research focused inside Syria and published over the course of the Syrian conflict. Methods As part of a broader scoping review covering English, Arabic and French literature on health and Syria published from 01 January 2011 to 31 December 2019 and indexed in seven citation databases (PubMed, Medline (OVID), CINAHL Complete, Global Health, EMBASE, Web of Science, Scopus), we analyzed conflict-related research papers focused on health issues inside Syria and on Syrians or residents of Syria. We classified research articles based on the major thematic areas studied. We abstracted bibliometric information, study characteristics, research focus, funding statements and key limitations and challenges of conducting research as described by the study authors. To gain additional insights, we examined, separately, non-research publications reporting field and operational activities as well as personal reflections and narrative accounts of first-hand experiences inside Syria. Results Of 2073 papers identified in the scoping review, 710 (34%) exclusively focus on health issues of Syrians or residents inside Syria, of which 350 (49%) are conflict-related, including 89 (25%) research papers. Annual volume of research increased over time, from one publication in 2013 to 26 publications in 2018 and 29 in 2019. Damascus was the most frequently studied governorate (n = 33), followed by Aleppo (n = 25). Papers used a wide range of research methodologies, predominantly quantitative (n = 68). The country of institutional affiliation(s) of first and last authors are predominantly Syria (n = 30, 21 respectively), the United States (n = 25, 19 respectively) or the United Kingdom (n = 12, 10 respectively). The majority of authors had academic institutional affiliations. The most frequently examined themes were health status, the health system and humanitarian assistance, response or needs (n = 38, 34, 26 respectively). Authors described a range of contextual, methodological and administrative challenges in conducting research on health inside Syria. Thirty-one publications presented field and operational activities and eight publications were reflections or first-hand personal accounts of experiences inside Syria. Conclusions Despite a growing volume of research publications examining population and humanitarian health and health systems issues inside conflict-ravaged Syria, there are considerable geographic and thematic gaps, including limited research on several key pillars of the health system such as governance, financing and medical products; issues such as injury epidemiology and non-communicable disease burden; the situation in the north-east and south of Syria; and besieged areas and populations. Recognising the myriad of complexities of researching active conflict settings, it is essential that research in/on Syria continues, in order to build the evidence base, understand critical health issues, identify knowledge gaps and inform the research agenda to address the needs of the people of Syria following a decade of conflict. Supplementary Information The online version contains supplementary material available at 10.1186/s13031-021-00384-3.


Introduction
The armed conflict in Syria is commonly described as being among the most extensively studied and documented of contemporary conflicts [1]. There is an expanding volume of literature on a diverse range of health issues relating to the conflict, from attacks on healthcare and use of chemical weapons to refugee health status assessment. Research in and on active conflict zones is inherently difficult, and these challenges are reflected in the focus, nature and volume of research outputs produced while an armed conflict is ongoing. For example, while the challenges facing the health systems of countries hosting large numbers of Syrian refugees have been documented [2,3], research assessments of the fragmented health system(s) inside war-torn Syria are limited. Similarly, compared with populations inside Syria, Syrian refugee populations are more accessible and therefore have received comparatively more research attention, including reviews and syntheses of this large volume of published research [4].
The Lancet -American University of Beirut Commission on Syria is an international research collaboration launched in December 2016 to analyse the Syrian conflict, its toll and the international response through a health and wellbeing lens, and to propose a set of recommendations to address current and future needs, inform rebuilding efforts and drive accountability [5]. To inform its work, the Commission has conducted a number of literature reviews. A paper examining clinical, biomedical, public health and health systems articles on Syria published between 1991 and 2017 reported that compared with the pre-conflict period (i.e. pre-2011), over the course of the conflict the number of healthrelated publications increased while the rate, type, topic and local authorship of publications changed. News, commentaries and editorial publications and not research largely drove the increase in publication volume during the conflict period [6]. Whilst non-research publications are crucial to raise awareness, rapidly disseminate information and inform advocacy during active conflicts, research in/on active war zones is also essential. To the best of our knowledge, a detailed thematic overview of conflict-related research on health inside Syria has not been published. Such a review is important to understand what themes, population subgroups and geographic areas have been examined, allowing identification of knowledge gaps to inform the health research agenda. In this paper, we aim to characterise conflictrelated population and humanitarian health and health systems research focused inside Syria and published over the course of the conflict.

Search strategy
This study is a sub-analysis of a broader scoping review of literature published between 2011 and 2019 and examining human health and Syria or Syrians, including studies of refugees and multi-country publications that include but are not exclusively limited to Syria. This review is different to, and complements, the prior review by Abdul-Khalek et al. [6] in that it covers a larger set of issues, has a broader geographical scope (inside Syria, outside Syria, multicountry settings including Syria), covers exclusively the conflict years and over a longer time-span of the conflict, and has specifically examined publications by conflict and non-conflict-related status. The search strategy for the broader scoping review is provided in the Additional file 1. Briefly, the broader scoping review searched for literature on human health and Syria or Syrians published in English, Arabic or French from 1 January 2011 to 31 December 2019 and indexed in seven bibliographic and citation databases (PubMed, Medline (OVID), CINAHL Complete, Global Health, EMBASE, Web of Science, Scopus). After deduplication, 13,699 records were identified. Two-stage screening against pre-specified criteria by at least two reviewers, review of reference lists and review of additional papers known to the authors resulted in a total of 2073 relevant publications.
For this current analysis, we examined only conflictrelated research papers that studied health issues inside Syria and focused on Syrians or residents in Syria (e.g. Palestinian or Iraqi refugees). We defined conflictrelated publications as those examining the Syrian conflict, its effects or the conflict response. We defined research papers as publications of any type (including traditional research papers, letters, commentaries and other) that report on the primary collection of data, or the secondary analysis and interpretation of existing data. We therefore excluded review publications and literature syntheses, as well as non-conflict related publications (e.g. biomedical or genomic studies conducted during the war but not related to the Syrian conflict, its effects or the conflict response), clinical case studies and case series, conflict-related studies focused only on Syrians outside Syria (e.g. studies of Syrian refugees or studies of war casualties evacuated for treatment in neighbouring countries), and studies conducted in multiple countries that include Syria as one of any number of study countries. Field and operational activities publications, defined as papers describing operational activities or organizational field experiences inside Syria but not presenting research per se (e.g. papers describing set-up of a field facility and number of patients seen, or describing humanitarian operations), which provide important insights or data about health issues inside Syria during the conflict, were considered separately to the research papers. Similarly, personal reflections and narrative accounts of first-hand experiences inside Syria were considered separately. News reports and news interviews with personnel inside Syria were not included in this analysis.

Literature dataset analysis
We classified research articles into six categories based on the major thematic areas studied: mortality; population health status; health determinants and risks (including behavioural, physiological, environmental and social determinants of health); humanitarian assistance, response or needs (including any studies conducted by humanitarian agencies or analysis of services provided by humanitarian actors); health system (including papers examining any of the six health system pillars as defined by the World Health Organization [7], namely service delivery (unless delivered by humanitarian actors), health workforce, health information systems, medical products, financing, governance); and war strategies & alleged international humanitarian law (IHL) violations (including studies reporting on warfare, besiegement and related human rights violations, attacks on civilian infrastructures such as health facilities, and publications on chemical attacks). A single paper could be classified into multiple thematic categories if it had a major focus on more than one theme.
For each paper, at least one reviewer abstracted bibliometric information and study characteristics (including study description, study period, methodology, governorates/ geographic location of the study, study population, country of affiliation(s) of first and last authors, type of institutional affiliation(s) of first and last authors). We also extracted qualitative data on selected key limitations and challenges of conducting research as described by the authors, and categorized these as contextual (which we defined as including issues of safety, accessibility, stakeholder engagement and cultural considerations), methodological (including issues related to design and conduct of the study) or administrative (including issues related to research permits and permissions, logistics, research capacity). Where available, funding statements were also reviewed and assigned to one of three categories (funded, not funded, not reported). Classification of each paper was discussed by three reviewers.
We used basic descriptive statistics to summarise key bibliometric characteristics of the research papers and changes in the volume and focus of research over time. Key challenges encountered were summarized narratively.

Results
Among the 13,699 records initially identified through the full scoping review, 2073 papers were considered relevant to human health and Syria. For this conflictrelated research subanalysis, we excluded clinical case reports and case series (n = 169), publications that examined multiple countries of which Syria was one (n = 268), publications that studied Syrians outside Syria (n = 924), publications focussed inside Syria but not related to the conflict (n = 359) and conflict-related publications focussed inside Syria that were not research publications, personal reflections or descriptions of field and operational activities (n = 225). This resulted in a total of 89 conflict-related research publications focused inside Syria, which form the dataset of this analysis. These conflict-related research papers were all published in English. We also identified 31 English-language field and operational activities papers focused on health inside Syria and eight personal narrative reflections, which we examine separately. Table 1 presents summary characteristics of the 89 conflict-related research papers. The conflict in Syria started in 2011 but there were no conflict-related research papers published during 2011-2012. Thereafter the annual volume of research increased over time, from one publication in 2013, three in 2014, to 26 publications in 2018 and 29 in 2019. There is considerable variation in the governorates studied by thematic focus and over time (Table 1, Fig. 1). Damascus is the most frequently studied governorate (n = 33), followed by Aleppo (n = 25), Idlib (n = 20), Lattakia (n = 15) and Hama (n = 14). Deir Al Zour (n = 3), Quenietra (n = 3) and As-Sweida (n = 3) are the least frequently studied. Twelve papers have a national scope. Several papers do not identify specific governorates, instead referring to the controlling factions, describing for example opposition-  a Some studies cover multiple themes b Due to the fluid nature of the conflict and inconsistencies in reporting of study locations, we report here the governorates whenever they are reported by the study authors, regardless of political control (i.e. opposition-controlled, government-controlled or non-government-controlled). When the governorates are not specified but the political control of the study setting is reported by study authors, it is recorded as such in this table. Some studies report neither the political control nor the governorates, and these are denoted as 'not reported'. Some studies cover multiple governorates c Other includes Australia (1), Austria (1), Egypt (2), Israel (1), Japan (1), Qatar (2), Saudi Arabia (2) Papers have used a wide range of research methodologies, including primary quantitative methods (n = 40) such as surveys, questionnaires and clinical trials; secondary quantitative data analysis (n = 28) mainly using surveillance system, medical record or program data; and qualitative methodologies (n = 15). Six papers used mixed methods (Table 1).
For the majority of papers, the country of institutional affiliation(s) of first and last (assumed to be the senior) authors are Syria (n = 30, 21 respectively), the United States (n = 25, 19 respectively) or the United Kingdom (n = 12, 10 respectively). For 20 papers (22.4%), both first and last authors had a Syrian affiliation. The institutional affiliation of first authors was predominantly academic (including universities and university hospitals) (n = 69), followed by humanitarian organizations (n = 14), clinical facilities (n = 7), think tank or research organization (n = 2), United Nations (UN) agencies (n = 2), government (n = 1), military (n = 1) and independent (n = 1). The institutional affiliation of senior/ last authors was predominantly academic (n = 65), followed by humanitarian (n = 13) or clinical (n = 7) organisations, with a few senior authors affiliated to governmental or UN agencies (n = 2 for each), and military (n = 1). Of the 37 papers reporting a specific funding source, five listed Syrian universities as the funding source. Table 2 presents detailed summaries of each research paper.
Of these health status studies, a few also report on socioeconomic associations with disease burden [43,72,79,91], health seeking behaviours [84,93] and exposure to violence as a determinant of health [94]. Several other papers focus primarily on health determinants and risks, including neighbourhood socioeconomic status [9,68], occupational stress [59], food security [34], and smoking prevalence and smoking behaviours before and during the war [53].
Thirty-four research papers examine the various pillars of the health system. Research on health workforce includes studies of the prevalence of psychological symptoms and burnout among medical students and trainees                 [27,71], workforce training [42], interventions using social media platforms as a teaching medium [12], consideration of the impact of conflict on workforce size, support or wellbeing [17,25,40,49,80,85], including numbers of health workers killed or injured by attacks on health care [35,36,52], workforce wellbeing interventions [59], workforce requirements to address estimates of likely disease burden [20], and studies of medical student career plans [63] and attitudes to research [66].
Health information systems are studied largely in the context of communicable disease surveillance and comparison of surveillance systems covering government and non-government controlled areas [18,23,26,88]. Two papers cover issues of health system governance, one through key informant interviews with health service providers, donors and end-users in oppositioncontrolled areas [77] and the other through interviews with UNRWA personnel that included consideration of adaptive mechanisms used to ensure resilience and ongoing function of the UNRWA health system [85]. Medical products are the focus of two papers, one of which surveyed community pharmacists in Damascus and Damascus countryside (Rural Damascus) regarding prescription drug misuse and characteristics of patients seeking such medications [70], and the other considered impacts of conflict on the UNRWA system, including on availability of medicines and medical supplies [85]. There are no studies on health financing.
Humanitarian assistance, response or needs (which included any studies conducted or analysis of services provided by humanitarian agencies) are the focus of 26 papers. These include estimates of IDP numbers and trends [14], humanitarian needs assessments among the general population, many of whom were displaced, in nine predominantly government-controlled governorates in 2014 [13,14] and among the general population [48] and displaced and female-headed households in 10 largely urban government-controlled areas in 2016 [33]; identifying optimal locations for IDP shelters [82] and primary healthcare facilities [86] in Idlib based on beneficiary needs assessments and modelling; and a snapshot survey of community income and humanitarian assistance in Idlib [31]. Other studies included analysis of Qatar Red Crescent surveys of the impacts of the conflict on education, family and public health status [22] and diagnoses, injuries and comorbidities [41] among children in Northern Syria in 2015; and household surveys of water, sanitation and hygiene (WASH) and health outcomes in opposition-controlled Daraa and Quneitra in 2016-17 [65]. Review of humanitarian programmatic data and operations included middle-upper arm circumference screening, survey of living conditions and food security, and nutritional programming administered by Medecins Sans Frontiers (MSF) in Al-Raqqa in 2013 [10], MSF vaccine-preventable disease risk assessment, pre-and post-vaccine coverage surveys and immunization activity in Aleppo in 2015 [47], 2012-2014 surgical data from an MSF field hospital in Northwest Syria [19], blast injuries managed at an MSFsupported facility in Raqqa in 2017-18 [89], MSF paediatric consultations in Aleppo and Raqqa in 2013-16 [57], MSF assessment of health status of recently arrived IDPs in Al-Raqqa in 2017 [94], primary care services delivered by 10 Union of Medical Care and Relief Organisations (UOSSM) centres in opposition-controlled territories in 2014-2015 [28], and analysis of data from the humanitarian health response in contested and opposition-controlled areas in 2013-14 [32]. Additional interventions and program evaluations included delivery and evaluation of an intervention through provision of information and follow-up questionnaire in bread packages being distributed by a humanitarian organization in Northern Syria [21], evaluation of three modes of food assistance programming in Idlib in 2014-15 [34], evaluation of an International Rescue Committee cash assistance program on violence against women in Raqqa [76], evaluation of effectiveness of multi-level WASH risk reduction interventions in southern Syria in 2018 [64] and examination of the impact of a psychosocial support program on the wellbeing of a control and intervention group of farmers [96]. Several papers interviewed humanitarian workers, including humanitarian health staff working on non-communicable disease (NCD) care in Syria [50] and those involved in the cross-border humanitarian response from Turkey [78,81].
Fourteen papers research health issues related to war strategies and alleged IHL violations, including an expert panel review of YouTube videos following a sarin gas attack [11] and interviews with healthcare workers in opposition-controlled areas regarding attacks on healthcare and challenges and experiences in responding to chemical attacks [49]. Other research in this theme examined attacks on health care [35,36,52,67,90], areas under or the effects of siege [40,58,80], and war-related mortality [15,45,51,90] including a study of characteristics of deceased victims of a chemical weapons attack [62]. Mortality is the subject of ten papers, which report mortality counts provided by key informants in contested and opposition areas [32]; examine mortality data documented by the Violations Documentation Centre (VDC) [15,51,62]), examine associations between attacks on healthcare and civilian casualties [90] or confirm conflict events against war-related deaths from VDC in a fake-news dataset [69]; use capture-recapture methods on four datasets to estimate mortality in two governorates [16]; estimate the number of unique identifiable deaths by deduplicating four datasets [45]; use spatio-temporal death data to forecast conflict events [37] and report on a household survey of IDPs in Raqqa and retrospective one-year mortality, largely conflictrelated deaths [94].

Research themes by governorate
Themes studied vary by governorate (Table 1, Fig. 1). In Damascus, health status and the health system are the most frequently studied themes (n = 14 for each).
The health system was also the main theme examined in studies of Aleppo (n = 12) and Idlib (n = 9). Humanitarian assistance, response or needs are most frequently studied in the north-west of Syria, including Aleppo (n = 8), Idlib (n = 7) and Lattakia (n = 7), and of the studies examining specific governorates, all 14 governorates were covered in at least one paper. Of the papers examining war strategies and alleged IHL violations, the majority include a focus on Aleppo (n = 6) or Damascus (n = 5). On the national level, the health system is the most frequently studied theme (n = 8), followed by health status (n = 6), war strategies and alleged IHL violations (n = 4) and mortality (n = 3).

Research themes by author country of affiliation
Themes examined vary by country of affiliation of authors (Table 1). Authors with Syrian affiliations commonly publish on health status (n = 21 for first authors, n = 15 for last authors), the health system (n = 12 for first authors, n = 7 for last authors), and health determinants and risks (n = 6 for first authors, n = 5 for last authors), while the most frequently researched themes among US-affiliated authors are the health system (n = 11 for first authors, n = 10 for last authors), humanitarian assistance, response or needs (n = 9 for first authors, n = 3 for last authors), health status (n = 8 for first authors, n = 3 for last authors) and war strategies and alleged IHL violations (n = 6 for first authors, n = 8 for last authors).  Conflict context and safety and security considerations • impacting on accessibility [13,14,16,22,25,33,41,70,71]. • impacting selection of school study sites [60] • impacting ground team composition and generating reliance on local staff [21,47,61) • impacting ability to conduct research as planned, including delaying data collection [34]; requiring short data collection periods or terminating fieldwork earlier than planned [9,68]; postponing fieldwork [85]; requiring timing and setting of interviews that were often not conducive to research [9]; and impacting data collection [17] Ethical considerations due to the context • Assuring anonymization of data and / or locations, including for data integrity and participant / facility security [25,21] • Not including community representatives and other stakeholders in the study due to ethical concerns regarding security, anonymity and any potential risks of coercion regarding aid and services [85] • Study design considerations, including not using a control group in a clinical study of PTSD treatment in order to benefit as many as possible during wartime [56], and delivering a psychosocial intervention to the control group after completion of data collection [96] Researcher identity and relationship to the context • Wariness of researchers affiliated with western institutions [9,68] Participant recruitment, sample size Conflict context impacting availability of research subjects: • Conflict context potentially impacting willingness to participate [21,53,77,80] and requiring informal approaches to participants through trusted colleagues [9,68].  Field and operational activities publications Table 3 presents a summary of the 31 papers reporting on field and operational activities, of which 12 describe humanitarian assessment, responses or needs, including development of a rapid gender analysis tool [127], crossborder, sectoral and cluster coordination mechanisms [104,[115][116][117], and needs assessments and/or operational programming [98,105,[107][108][109][110]122]. Nineteen papers discuss various aspects of the health system, most commonly reporting on experiences of establishing and / or presentations to field hospitals [99][100][101]103], or establishing or delivering specific services including renal [102,112], dental [106], mental health [113], obstetric [111], maternal and child health [119], tele-cardiology [120], tele-intensive care [114,121], tele-radiology [118,123] and polio outbreak response activities [124]. Other papers described the national tuberculosis control program [125], activities of Syrian expatriate medical associations in supporting the health system, including through training, establishment of hospitals and provision of telemedicine services [97], and translation and uptake of an online medical education platform into Arabic by Syrian medical students [126]. War strategies and alleged IHL violations are the secondary theme of two papers, one describing experiences in besieged settings [123] and one paper reporting birth outcomes by chemical weapons exposure status for pregnant women seen at Al Ghouta hospital in late 2014 [111]. Only 12 (39%) of these field and operational activities publications are first-authored by an author with a Syrian affiliation. Of the 21 publications with multiple authors, only 5 (24%) had a senior (last) author with a Syrian affiliation.

Narrative personal reflections
Eight publications were reflections or first-hand personal accounts of experiences inside Syria. These included reflections of an expatriate physician on missions to field hospitals [128] including in Aleppo in 2013 [129]; experiences of a resident physician working in the neurosurgery department of a hospital under siege in Aleppo [130]; experiences of a medical resident working in Aleppo University Hospital following a chemical weapons attack, including reports of number of patient household deaths [94] • Selection and respondent biases impacting representativeness; limited generalizability due to restricted geographic access and because not all governorates impacted by war to the same extent and in the same way [27,33,48,49] • Potential for data collection and categorization to be biased by motivations of researchers, political or advocacy groups [51] Data availability and quality • Missing data and limited data availability [20,28,74] • Impact on data quality and availability due to patient care taking precedence over documentation during crisis [89] • Difficulties of ascertaining casualty counts in an active conflict [90] • Extracting additional data on war injuries limited as names were deleted from paper medical records for security reasons [74] • Difficulties with outcome measurement and follow up data, including inability to return for follow up because of security issues, inability to follow up by phone because of disrupted phone network [19] • Difficulties ascertaining response rate due to inability to contact participants directly, reliance on third party [24] • Absence of / difficulties with establishing population denominator [32,38,57,61] • Inability to validate authenticity of data collected from online video sources [11] presentations and outcomes [131]; experiences of medical volunteers during a mission in Idlib [132]; and personal and professional experiences of a Syrian neurosurgeon working in Syria [133]. Two papers are experiences of medical students, one reporting experiences undertaking research and accessing research training [134] and another reporting experiences of studying medicine in conflict [135].

Challenges reported in researching Syria
Researchers note a range of considerations and challenges of conducting research in/on Syria (Table 4).
Contextual challenges are largely related to safety and security issues, including the impact of conflict on access, often being limited to specific governorates or relatively safer areas, and conflict events impacting the ability to conduct research as planned.
Researchers report numerous methodological challenges, including limited data availability and access, data quality and completeness concerns, lack of population denominator data, and potential for bias at all stages of the research process.
Administrative considerations are largely related to securing permissions to conduct research and ethical review board processes, most notably the absence of such formal in-country governance structures. Conflict also impacted other aspects of research administration, including the availability of research funding.

Discussion
Although increasing over time, our analysis shows that a relatively limited number of research studies focused on health or populations inside Syria have been published over the course of the conflict to 2019. There are several geographic and thematic information gaps which likely reflect a myriad of factors, including issues of access and other challenges of conducting research during active conflict. There is a relative paucity of research on several key pillars of the health system such as governance, financing and medical products, and on a number of critical population health issues such as NCDs. Research coverage of governorates shows a heavy emphasis on Damascus and the north-west, with comparatively little research covering the north-east and the south of Syria. Our analysis does not identify any research on some specific vulnerable populations such as those currently or formerly imprisoned or detainees, and very few studies of besieged areas.

Some thematic areas have received limited research attention
Health status is the most frequently researched theme, with communicable diseases the most common focus. Given the disruption of health and social infrastructures during conflict, with attendant impacts on communicable disease surveillance and control, and the global health threat posed by outbreaks of communicable diseases such as polio, it is not surprising that communicable disease epidemiology and control is a major focus of research attention. Similarly, mental health is the focus of several papers which cover a number of population subgroups, including medical students [27], women [79,91], children [56,60,83], selected patient populations [55], and IDPs [39,94], in addition to modelling estimates of disease burden and associated workforce requirements for the general population [20]. This is a crucial area of research in a conflict context and in a cultural setting where mental health issues remain stigmatized.
Other direct health effects of conflict receive comparatively little research attention. For example, injury epidemiology is covered in just five papers, three of which described a cohort of inpatients with abdominal [29], paediatric chest [46] or blast injuries [89]. Understanding injury epidemiology is critical to informing health and social system needs, both to address immediate acute care needs but also to inform estimates of likely disability burden in future and requirements for health and social infrastructures. This limited research focus may reflect data gaps due to lack of research infrastructure and/or prioritization of lifesaving provision of care above recordkeeping in acute emergencies and mass casualty events. The referral of many wounded individuals for treatment in neighboring countries may have also contributed to this gap, supported by an observation from our broader scoping review that there is more injury research from Turkey, Israel and Jordan than there is from within Syria.
NCDs are another major research gap, despite being identified as such in 2015 and a call for action issued [136]. Prior to conflict onset, Syria was advancing in its demographic and epidemiological transition, with NCDs dominating disease burden and health expenditure [137]. Left unaddressed and due to disruptions to the health system and altered health behaviours and preventive measures, this underlying disease burden is likely to have magnified. Studies among Syrian refugees indicate a high NCD burden [138]; a similar high burden likely exists among populations inside Syria. This warrants urgent research attention.
For a protracted conflict that has caused a large number of deaths, surprisingly few research studies have examined mortality. Notably, most of the mortality research considers direct war-related deaths. Few studies report on general mortality or examine indirect conflictrelated deaths, such as those due to treatment forgone and service unavailability, for instance cancer deaths due to lack of access to chemotherapy or end-stage renal failure deaths due to lack of dialysis services (one paper provides an anecdotal estimate of renal deaths for one centre [17]). Such information is essential at the facility, governorate and national levels, both to inform immediate needs and to drive accountabilitythe effects of war, and the impacts of atrocities such as killing a doctor or attacking a hospital, extend far beyond the immediate acute losses.
Accurately estimating mortality in conflict presents numerous challenges [16] and several factors may explain the relative paucity of mortality research in Syria. Human rights organizations tracking deaths, such as VDC, are reliant on ground reporters, but relative inaccessibility of some geographic areas influences data collection and completeness. Local researchers based inside Syria may find it difficult to investigate this sensitive issue. Insecurities may render conducting household assessment on representative samples difficult, or generate security threats to families, witnesses or data collectors. In some instances, there may be no witnesses left to report the deaths [16]. Disruption of health information infrastructure means limited availability and completeness of data from official local sources such as hospital records and vital registration data. The fact that the United Nations stopped officially reporting deaths in Syria since 2014 introduced a further barrier to rigorous mortality analyses. Mortality data are also highly politicised. Recognising the data limitations and challenges, there is a clear need to advance methods for researching mortality in conflict, including developing better estimates of mortality considering the difficulty in enumerating deaths (numerator) in a highly charged political environment and the changing population numbers (denominator) due to displacement.
War strategies and IHL violations are the focus of several papers, including those examining attacks on health care, effects of siege, and chemical weapons attacks. Attacks on health care in Syria have been well documented, both by the research community as well as by a number of human rights and humanitarian organisations. There are numerous methodological and contextual challenges to such research. Issues noted among the studies in this review included concerns about validation of reported data on either chemical weapons or attacks on healthcare infrastructure and personnel [11,35,52,67]. Reporting commonly depends on ground reporting systems which are subject to their own inherent limitations [35,67].
The limited research on key health system pillars, namely governance, financing and medical products, is also of concern, particularly as governance and financing are critical to any consideration and planning for health system rebuilding.

There is geographic variation in research volume and thematic issues examined
Focus of research covering areas such as Damascus, a Syrian government stronghold, is heavily on population health status and the health system, while research on northwest Syria (Aleppo and Idlib) focused more on the health system, particularly attacks on healthcare and other IHL violations, and humanitarian needs and assistance. Research on northeast Syria is extremely limited, and no research specifically on non-government controlled areas controlled by IS was identified in this review. These findings likely reflect security and access issues, in addition to conflict events and operational needs on the ground. For example, international agencies and humanitarian organizations based in Turkey have access to the opposition-controlled areas of north/ northwest Syria, directly or through Syrian/diasporic health and humanitarian organizations, including through cross-border assistance operations. This may facilitate access to populations and humanitarian providers and collection of data.
It is important to note that not all geographic areas of Syria have been impacted to the same extent and in the same ways by the conflict. Further, prior to the conflict there was considerable geographic variation in Syria's health system infrastructures, workforce distribution and resourcing [139], and demographic and population health profiles also varied across the country. Current population and humanitarian health issues and research needs therefore likely vary across Syria; such variation is not captured in this quantitative thematic assessment of number of research studies conducted per governorate. Future research should seek to identify the specific health research needs within and between governorates.

Vulnerable groups and hard-to-reach populations receive limited research attention
There is limited research on some specific population subgroups. The protracted conflict has resulted in chronic and large-scale displacement inside Syria, with over 6 million IDPs [140]. New displacements are still occurring. It is estimated that 2.5 million Syrians were subjected to siege at some point during the conflict [141]. It is reported that to March 2021, more than 149, 000 Syrians had been detained or forcibly disappeared [142]. These highly vulnerable populations are rarely studied. For example, only three papers [40,58,80], one field and operational activities publication [123] and one personal narrative [130] covered issues of siege. Understanding the health status and humanitarian needs of such populations is essential in order to inform programmatic action.
Novel methodologies have been applied to study health in an active conflict zone Numerous challenges are reported in the conduct of this body of research, largely consistent with those described by researchers who have worked in and studied a range of other active conflict zones. These include issues of access, data quality, quantity and availability (including lack of denominator data due to ongoing population displacement), and security considerations, including impacts on participant willingness to engage. A number of novel tools and methodologies were developed and described in this literature in order to overcome research constraints and to study conflict-related health issues. Humanitarian interventions have been used to piggyback health messaging and research. For instance, El-Khani et al. distributed parenting psychosocial support information and questionnaires in humanitarian bread deliveries [21], highlighting the scope for existing humanitarian routes to both distribute information and serve as a research platform. Social media is increasingly used as a research tool, including in conflict settings. Research included in this review has used social media in a number of ways, including as a data collection tool [8,11] and as a platform for delivery of an educational intervention [12]. Communication technologies have also been incorporated into research approaches, including through use of services such as WhatsApp as part of a tool to monitor attacks on healthcare in Syria [35], and secure messaging platforms used for remote interviews and data collection, including to overcome security considerations and access constraints [49,77,80].

Strengthening academic and operational research collaboration is important
For the majority of research publications, the institutional affiliations of first and/or last authors are academic (universities or university hospitals). A limited number are authored by individuals with a humanitarian organizational affiliation. Only a few papers had a mix of first/last authors from both academic and humanitarian organisations. Humanitarian organisations have a critical role to play in conducting policy-and practice-oriented research [143]. Strengthening academic-operational research collaboration is important, including for issues of data access and data sharing. For instance, much service provision data, however (in)complete, is held by humanitarian organizations, international agencies and government bodies. Sharing of information with researchers for secondary data analysis is often a fraught process. Bridging this information divide and encouraging collaboration between researchers and operational organisations might minimize duplication of effort, increase relevance of the research to the endusers and help ensure best outcomes for the populations who must be the ultimate beneficiaries of research. Humanitarian agencies also often have readier access to study populations than do academics. Academic researchers may face additional barriers to timely information dissemination; even when data are available to researchers, lengthy institutional processes, research governance mechanisms, protracted times to data access and peer-reviewed publication times may mean that data cannot actually be used and published in a timely manner to inform operational and policy activity.
Academic-humanitarian research partnerships may help address such barriers. For example, from the Syrian refugee context in Lebanon, an academic-humanitarian-public health authority research collaboration utilizing the complementary skills and expertise of each partner has ensured a successful and comprehensive project approach [144].
In this study we also identified a number of nonresearch publications reporting on operational and field activities and personal reflections. Such sharing of experiences should be encouraged, including by journals and journal editors.

Efforts to mitigate potential barriers to Syrian-led research in and on Syria warrant attention
This review shows good representation of first and last authors from Syrian institutions, with approximately a third of first authors and almost a quarter of last authors having Syrian institutional affiliations. This does not reflect the total number of first and last authors from Syria or with Syrian background, as conflict-related displacement of Syrian academics means that some are publishing but are now affiliated with institutions in countries outside Syria.
There are several potential barriers to Syrian researcher engagement which warrant attention. These include general difficulties in access and insecurities, limited supply and/or capacity of Syrian researchers based inside Syria, and disruption or collapse of research infrastructure in Syrian institutions, including through recurrent attacks on universities, and widespread oppression of academics and freedom of speech more broadly which have had a detrimental impact on higher education institutions in Syria [145,146]. Additionally, capacity building and training opportunities are limited: one study in this review reports lack of adequate training, research facilities and mentorship as barriers to research among undergraduates [66] and others also describe additional resource and funding constraints [134].
Such potential barriers to local research production must be addressed. Utilization of various techniques, e.g. use of pseudonyms to address security concerns, and implementation of contextually appropriate capacity building initiatives and frameworks, such as that proposed by others [147], to support more Syrian researchers and Syrian institutions to lead research on the health issues affecting their country and its people, is warranted.

Strengths and limitations
To the best of our knowledge, this is the first review to characterize the body of published research indexed in the main citation databases and examining health inside Syria over the course of the conflict. Themes assigned reflect a paper's major focus and do not necessarily capture all issues covered in a given publication. Assignment of key themes is necessarily subjective, and some papers may cover multiple thematic areas. Some of the themes are not mutually exclusive but were presented in distinct categories to highlight conflict-related gaps. For example, health-related IHL violations such as attacks on healthcare are determinants of health but specific to conflict settings; we therefore considered them in a separate category to the 'health determinants and risks' category, which captures traditional behavioural, physiological, environmental and social determinants of health that are also present in non-conflict zones. The scope of this paper is restricted to population and humanitarian health and health systems research, so studies of war strategies and IHL violations are limited to health-related violations and do not include publications examining attacks on non-health civilian infrastructures such as schools and bakeries, which are also upstream determinants of health.
Notably, this quantitative assessment of number of research studies conducted per governorate does not take into account research qualitya single high quality study may provide greater and more useful information than multiple lower quality and less rigorous publications.
Our summary of key challenges described in the papers is not an exhaustive list of all limitations noted by the authors but rather captures the main and frequently described issues. Relevant studies may have been excluded, or missed if published in journals not indexed in the seven bibliographic databases searched. For example, Arabic language papers published in local or regional journals are not captured in this review. Our search did not include the grey literature, so the findings of this review likely to do not fully capture all operational and field research undertaken and published by humanitarian organisations. Additionally, research may be undertaken to inform policymaking or programmatic action but not published. Finally, academic research is often subject to a publication lag, so it is possible that some of the information gaps identified in this review are the subject of current work and forthcoming research publications.

Conclusions
Whilst there is a growing body of research examining population health issues inside conflict-ravaged Syria, there are considerable geographic and thematic gaps, and issues and populations that warrant focused research attention. Recognising the myriad of complexities of researching active conflict zones, including issues of data completeness, coverage and politicisation, it is essential that research in and on Syria continues, in order to build the evidence base and inform policy and programmatic actions that are required to protect and promote health in Syria following a decade of conflict.